PAUF promotes adhesiveness of pancreatic cancer cells by modulating focal adhesion kinase

Abstract

Pancreatic cancer is a notorious disease with a poor prognosis and low survival rates, which is due to limited advances in understanding of the molecular mechanism and inadequate development of effective treatment options over the decades. In previous studies, we demonstrated that a novel soluble protein named pancreatic adenocarcinoma up-regulated factor (PAUF) acts on tumor and immune cells and plays an important role in metastasis and progression of pancreatic cancer. Here we show that PAUF promotes adhesiveness of pancreatic cancer cells to various extracellular matrix (ECM). Our results further support a positive correlation of activation and expression of focal adhesion kinase (FAK), a key player in tumor cell metastasis and survival, with PAUF expression. PAUF-mediated adhesiveness was significantly attenuated upon blockade of the FAK pathway. Moreover, PAUF appeared to enhance resistance of pancreatic cancer cells to anoikis via modulation of FAK. Our results suggest that PAUF-mediated FAK activation plays an important role in pancreatic cancer progression.

Silencing of pancreatic adenocarcinoma upregulated factor by RNA interference inhibits the malignant phenotypes of human colorectal cancer cells

“…PAUF also plays important roles in cancer progression, including cell proliferation, adhesion, migration and invasion (20)(21)(22)(23). In our present study, we detected the expression levels of PAUF in 48 cases of CRC by using real-time RT-PCR.…”

Discovery, Primary, and Crystal Structures and Capacitation-related Properties of a Prostate-derived Heparin-binding Protein WGA16 from Boar Sperm

“…Sequence homology indicates that WGA16 is closer to human and pig ZG16b than human ZG16p. A recent study (66) reported that ZG16b facilitates tumor growth and metastasis through enhancing cell adhesiveness by regulating interactions between tumor cells and extracellular matrix molecules.…”

A PAUF-neutralizing antibody targets both carcinoma and endothelial cells to impede pancreatic tumor progression and metastasis

“…1E). Moreover C-X-C chemokine receptor 4 (CXCR4) expression, induced by PAUF and proposed to be associated with enhanced metastasis of carcinoma cells [20], was also reduced by PMAb83. These data indicate that PMAb83 can effectively impair in vivo tumor progression and metastasis by specifically targeting PAUF.…”

“…Based on our previous observations that PAUF strengthens the cancer-associated traits of PDAC cells [19,20], we next explored the effects of PMAb83 at the cellular and molecular levels. dose-dependent manner ( Fig.…”

“…Moreover, PAUF positively expresses in majority of patients with pancreatic cancer, suggesting its roles in pancreatic cancer development [19]. Functioning as an autocrine factor, varied PAUF levels result in altered migration, invasion, proliferation, and adhesion of pancreatic carcinoma cells [19][20][21] and correlate with the metastasis of the cells to distant organs in orthotopically xenografted mouse models [19]. In paracrine manners, PAUF creates a microenvironment favorable for tumor progression and metastasis.…”